This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to explore the potential for application of identified innate agonists in fighting Dengue virus (DV) infection. DV is an Category A pathogen and an important emerging disease threat worldwide, with no available vaccine and very few treatment and/or preventative options. We have determined that a plant-derived compound contained in a dietary supplement can reduce DV titers in infection of human peripheral blood mononuclear cells (PBMCs) in vitro. We hypothesized that treatment with the compound would enhance the anti-viral state of infected cells. DV-infected human PBMCs treated with the compound increase expression of a critical antiviral gene product in the type I interferon (IFN) pathway. In addition to enhancing innate immune responses of cells, the oligomeric, but not monomeric, forms of the compound also had direct antiviral activity. Although there were several challenges to overcome, we have developed and begun to work with an immunocompetent mouse model of DV infection. A monoclonal antibody specific for DV that enhanced infection in immune deficient mice will now be applied in the immunocompetent DV infection model. Antibody-enhanced immunocompetent mouse models of DV infection will be utilized to determine the feasibility of oral treatment with the supplement.